The long-term goal of this research is to gain knowledge about mechanisms which determine the radiosensitivity of mammalian cells, particularly those involved in the response of stationary or very slowly proliferating cells to X-irradiation. We will utilize density-inhibited plateau phase cultures of several different cell strains including 10T-1/2 mouse embryo cells, human diploid cells and human tumor cells. Three endpoints will be studied in parallel: cell survival; malignant transformation in vitro; and mutation rate. We will investigate the relationships between these cellular effects and try to correlate them with molecular DNA repair processes. Several differences have been observed between the X-ray response of stationary and exponentially growing cells, notably in the ability of stationary cells to repair potentially lethal radiation damage (PLD) if allowed to remain in a resting phase of growth for several hours. The enhancement of survival which occurs during PLD repair is, however, associated with enhancement of malignant transformation. The relationship between survival and transformation will be studied by use of factors known to influence survival such as incubation at low temperature or with dinitrophenol (which markedly enhances the survival of stationary cells), exposure to high LET and split-dose irradiation, and by studying UV transformation. Molecular repair processes will be investigated in synchronized cells and plateau phase cultures, and evidence will be sought for their role in PLD repair. Experiments will be continued to isolate and study cells mutant in their response to radiation and in their DNA repair capacity. In all of these studies, an overall objective is to understand and correlate events such as repair at the molecular level with cellular effects such as survival and malignant transformation. BIBLIOGRAPHIC REFERENCES: Terzaghi, M. and J. B. Little. Oncogenic transformation in vitro by X-rays: Influence of repair processes. Chapt. 27 in: The Biology of Radiation Carcinogenesis, edited by J. B. Yuhas, R. W. Tennant and J. B. Regan, Raven Press, N. Y., 1976, pp 327-334. Weichselbaum, R. R., J. Epstein, J. B. Little and P. L. Kornblith. In Vitro cellular radiosensitivity of human malignant tumors. Europ. J. Cancer 12: 47-51, 1976.